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CD73(+) adipose-derived stem cells reduce scar formation through PLOD1

BACKGROUND: Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC thera...

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Autores principales: Xu, Miao, Fang, Shuo, Ma, Xiaorong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848413/
https://www.ncbi.nlm.nih.gov/pubmed/35282129
http://dx.doi.org/10.21037/atm-21-6557
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author Xu, Miao
Fang, Shuo
Ma, Xiaorong
author_facet Xu, Miao
Fang, Shuo
Ma, Xiaorong
author_sort Xu, Miao
collection PubMed
description BACKGROUND: Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely through modulating macrophage polarization. In the present study, we tested whether a CD73(+) subpopulation of AMSCs could reduce scar formation compared with CD73(–) AMSCs. METHODS: The gene profile of CD73(+) versus CD73(–) AMSCs was obtained from a validated public database, GSE167219. AMSCs were isolated from adipose tissue surrounding the groin of mice, after which CD73(+) versus CD73(–) AMSCs were sorted using flow cytometry. PLOD1 levels were determined in CD73(+) versus CD73(–) AMSCs. Then, PLOD1 in CD73(–) AMSCs was depleted by a short-hair interfering RNA against PLOD1 (sh-PLOD1), while PLOD1 in CD73(+) AMSCs was increased by expression of a PLOD1 transgene. A blade was used to induce a skin injury on the middle back of the mice. Either CD73(+) AMSCs or CD73(+) PLOD1 AMSCs or CD73(–) AMSCs or CD73(–) sh-PLOD1 AMSCs were intravenously transplanted into the injured region of the mice. Fibrosis and the underlying mechanisms were investigated. Co-immunoprecipitation was performed to evaluate interaction between CD73 and PLOD1. RESULTS: CD73(+) AMSCs expressed significantly lower levels of PLOD1, a potent stimulator of fibrosis, compared with CD73(–) AMSCs. Transplantation of CD73(+) AMSCs generated significantly reduced fibrosis at the skin injury site compared with CD73(–) AMSCs. However, expression of PLOD1 in CD73(+) AMSCs abolished its advantageous effects on fibrosis reduction, while depletion of PLOD1 in CD73(–) AMSCs improved the outcome of fibrosis to the levels of transplantation of CD73(+) AMSCs. Co-immunoprecipitation showed no direct protein interaction between CD73 and PLOD1. CONCLUSIONS: CD73(+) AMSCs are a subgroup of AMSCs with better therapeutic effects on wound healing, and can inhibit scar formation through reduced PLOD1 in an indirect manner.
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spelling pubmed-88484132022-03-10 CD73(+) adipose-derived stem cells reduce scar formation through PLOD1 Xu, Miao Fang, Shuo Ma, Xiaorong Ann Transl Med Original Article BACKGROUND: Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely through modulating macrophage polarization. In the present study, we tested whether a CD73(+) subpopulation of AMSCs could reduce scar formation compared with CD73(–) AMSCs. METHODS: The gene profile of CD73(+) versus CD73(–) AMSCs was obtained from a validated public database, GSE167219. AMSCs were isolated from adipose tissue surrounding the groin of mice, after which CD73(+) versus CD73(–) AMSCs were sorted using flow cytometry. PLOD1 levels were determined in CD73(+) versus CD73(–) AMSCs. Then, PLOD1 in CD73(–) AMSCs was depleted by a short-hair interfering RNA against PLOD1 (sh-PLOD1), while PLOD1 in CD73(+) AMSCs was increased by expression of a PLOD1 transgene. A blade was used to induce a skin injury on the middle back of the mice. Either CD73(+) AMSCs or CD73(+) PLOD1 AMSCs or CD73(–) AMSCs or CD73(–) sh-PLOD1 AMSCs were intravenously transplanted into the injured region of the mice. Fibrosis and the underlying mechanisms were investigated. Co-immunoprecipitation was performed to evaluate interaction between CD73 and PLOD1. RESULTS: CD73(+) AMSCs expressed significantly lower levels of PLOD1, a potent stimulator of fibrosis, compared with CD73(–) AMSCs. Transplantation of CD73(+) AMSCs generated significantly reduced fibrosis at the skin injury site compared with CD73(–) AMSCs. However, expression of PLOD1 in CD73(+) AMSCs abolished its advantageous effects on fibrosis reduction, while depletion of PLOD1 in CD73(–) AMSCs improved the outcome of fibrosis to the levels of transplantation of CD73(+) AMSCs. Co-immunoprecipitation showed no direct protein interaction between CD73 and PLOD1. CONCLUSIONS: CD73(+) AMSCs are a subgroup of AMSCs with better therapeutic effects on wound healing, and can inhibit scar formation through reduced PLOD1 in an indirect manner. AME Publishing Company 2022-01 /pmc/articles/PMC8848413/ /pubmed/35282129 http://dx.doi.org/10.21037/atm-21-6557 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Xu, Miao
Fang, Shuo
Ma, Xiaorong
CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title_full CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title_fullStr CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title_full_unstemmed CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title_short CD73(+) adipose-derived stem cells reduce scar formation through PLOD1
title_sort cd73(+) adipose-derived stem cells reduce scar formation through plod1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848413/
https://www.ncbi.nlm.nih.gov/pubmed/35282129
http://dx.doi.org/10.21037/atm-21-6557
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